Ionic Mechanisms of Desflurane on Prolongation of Action Potential Duration in Rat Ventricular Myocytes

PURPOSE: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes. MATERIALS AND METHODS: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K+ current (I(to)), sustained outward current (I(sus)), inward rectifier K+ current (I(KI)), and L-type Ca2+ current were determined using a whole cell voltage clamp. RESULTS: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20+/-8% and 32+/-7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca2+ current by 40+/-6% (p<0.05). CONCLUSION: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing Ito in rat ventricular myocytes.

Potassium channels in health, disease & development of channel modulators.

Ion channels present in the plasma membrane and intracellular organelles of all cells, play an important role in maintaining cellular integrity, smooth muscle contraction, secretion of hormones and neurotransmitters. Among the ion channels, potassium channels (K+) are the most abundant having important role in cardiac repolarization, smooth muscle relaxation and insulin release. These are also involved in the regulation of physiological functions like gastrointestinal peristalsis. These channels are the most diverse of all ion channels and are coded by at least 75 genes. Moreover, these have different subunits which co-assemble to form diverse functional channels. Abnormalities in K+ channels are associated with diseases like long QT syndrome, Anderson Tawil syndrome, epilepsy, type 2 diabetes mellitus, etc. A number of naturally occurring as well as synthetic compounds have been identified that modulate the opening and closure of KATP Channels. Some of the currently available K+ channel modulators like sulphonylureas, minoxidil, amiodarone, etc. lack tissue selectivity and have adverse effects. Hence, the success of KATP channel modulators depend on their tissue selectivity. Molecular level studies are needed to understand the type of K+ channels as this can lead to the development of newer drugs with tissue selectivity for various diseases.

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression.

Effect of some ions on sperm activation in Brycon henni(Eigenmann 1913)

Spermatozoa in Characid fish remain immobile in seminal plasma and are activated when freed into water where the ionic balance seems to be the main factor starting the activation process. This process was the target of the present study with emphasis on the activation of motility and on motility maintenance over time. The effect of isosmotic solutions was analyzed taking into account the possible combinations of the following ions, Ca2+, K+, Mg2+ and Na+ as well as the effect of channel blocking agents. The parameters measured were cells with motility (per cent), duration of motility (s), plasma membrane potential, and the effect of channel blockers on activation time and on motility. There was an increased motility when the semen was incubated in solutions containing K+ (p<0.05) compared with the control (CaNaMgK solution); the longest duration of motility was attained when the incubation was performed in solutions containing Na+ and Mg2+ (p<0.05). All solutions induced a change in membrane potential detected after 15 s of activation. Blocking K+, Ca2+ and Na+ channels did not alter motility but decreased the activation time (p<0.05). Potassium induced activation at all concentrations up to 105 mM, but motility was drastically decreased at concentrations higher than 140 mM (p<0.05). The conclusion is that interaction of the ionic environment with the cell membrane leads to changes in membrane potential and intracellular signalling that trigger sperm motility in Brycon henni.

Nuevas perspectivas en el síndrome de QT largo / New perspectives in long QT syndrome

Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk to sudden death secondary to ventricular dysrrhythmias. Was the first cardiac channelopathy described and is probably the best understood. After a decade of the sentinel identification of ion channel mutation in LQTS, genotype-phenotype correlations have been developed along with important improvement in risk stratification and genetic guided-treatment. Genetic screening has shown that LQTS is more frequent than expected and interestingly, ethnic specific polymorphism conferring increased susceptibility to drug induced QT prolongation and torsades de pointes have been identified. A better understanding of ventricular arrhythmias as an adverse effect of ion channel binding drugs, allow the development of more safety formulas and better control of this public health problem. Progress in understanding the molecular basis of LQTS has been remarkable; eight different genes have been identified, however still 25% of patients remain genotype-negative. This article is an overview of the main LQTS knowledge developed during the last years.

El síndrome de QT largo (SQTL) es una canalopatía que genera grave alteración en la repolarización ventricular predispone a arritmias malignas y muerte súbita. Fue la primera canalopatía arritmogénica descrita y quizá la mejor entendida hasta ahora. Transcurrida ya más de una década de la identificación de la primera mutación asociada al SQTL, se ha hecho evidente que este trastorno es mucho más frecuente de lo que inicialmente se pensaba; los avances en el conocimiento de la fisiopatología molecular de esta enfermedad han permitido hacer una correlación genotipo-fenotipo, optimizando el tratamiento y permitiendo estratificar el riesgo en forma precisa. Se ha logrado entender con mayor detalle los efectos adversos de distintas drogas que interactúan con los canales iónicos, permitiendo así generar fármacos más seguros y, en su defecto, monitorizar de cerca aquellos que a pesar de tener este efecto adverso, es necesaria su administración. Los avances son importantes pero no todo está dicho, 25% de los casos no tienen mutaciones en los genes descritos hasta la fecha, por lo que el SQTL continúa siendo motivo de investigación. El presente artículo constituye un resumen de los principales conceptos desarrollados en los últimos diez años que han sido cruciales en el manejo de esta enfermedad.

Sodium-activated Potassium Current in Guinea pig Gastric Myocytes

This study was designed to identify and characterize Na+ -activated K+ current (I(K(Na))) in guinea pig gastric myocytes under whole-cell patch clamp. After whole-cell configuration was established under 110 mM intracellular Na+ concentration ([Na+]i) at holding potential of -60 mV, a large inward current was produced by external 60 mM K+([K+] degree). This inward current was not affected by removal of external Ca2+. K+ channel blockers had little effects on the current (p>0.05). Only TEA (5 mM) inhibited steady-state current to 68+/-2.7% of the control (p<0.05). In the presence of K+ channel blocker cocktail (mixture of Ba2+, glibenclamide, 4-AP, apamin, quinidine and TEA), a large inward current was activated. However, the amplitude of the steadystate current produced under [K+]degree (140 mM) was significantly smaller when Na+ in pipette solution was replaced with K+ - and Li+ in the presence of K+ channel blocker cocktail than under 110 mM [Na+]i. In the presence of K+ channel blocker cocktail under low Cl- pipette solution, this current was still activated and seemed K+ -selective, since reversal potentials (E(rev)) of various concentrations of [K+]degree-induced current in current/voltage (I/V) relationship were nearly identical to expected values. R-56865 (10-20 microgram), a blocker of IK(Na), completely and reversibly inhibited this current. The characteristics of the current coincide with those of IK(Na) of other cells. Our results indicate the presence of IK(Na) in guinea pig gastric myocytes.

Involvement of potassium channels in hypoglycemic effect of sertraline.

Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline.

Mitochondrial K+ transport and cardiac protection during ischemia/reperfusion

Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK ATP) are strongly cardioprotective under these conditions. Furthermore, mitoK ATP are physiologically activated during ischemic preconditioning, a procedure which protects against ischemic damage. In this review, we discuss mechanisms by which mitoK ATP may be activated during preconditioning and the mitochondrial and cellular consequences of this activation, focusing on end-effects which may promote ischemic protection. These effects include decreased loss of tissue ATP through reverse activity of ATP synthase due to increased mitochondrial matrix volumes and lower transport of adenine nucleotides into the matrix. MitoK ATP also decreases the release of mitochondrial reactive oxygen species by promoting mild uncoupling in concert with K+/H+ exchange. Finally, mitoK ATP activity may inhibit mitochondrial Ca2+ uptake during ischemia, which, together with decreased reactive oxygen release, can prevent mitochondrial permeability transition, loss of organelle function, and loss of physical integrity. We discuss how mitochondrial redox status, K+ transport, Ca2+ transport, and permeability transitions are interrelated during ischemia/reperfusion and are determinant factors regarding the extent of tissue damage.

Sex difference in the repolarization currents of rabbit ventricular cells / 华中科技大学学报（医学）（英德文版）

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4+/-26.5 ms, n=15) than in male ones (489.0+/-20.7 ms, n = 14), P0.05). The lower IK.tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors

We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 æM and Emax of 100 percent (N = 10) or 20 æM and Emax of 92 percent (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 + or - 7.0, 43 + or - 3.9 and 78 + or - 5.6 percent) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 æM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 æM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 + or - 12 percent. Glibenclamide (1 or 3 æM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 æM), a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 æM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 æM, while methylene blue (10 or 30 æM) or ODQ (1 æM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 æM), a VIP receptor antagonist, significantly inhibited (37 + or - 7 percent) relaxation induced by gentisic acid, whereas CGRP (8-37) (0.1 æM), a CGRP antagonist, only slightly enhanced the action of gentisic acid.

Salt-induced hypertension in rats alters the response of isolated aortic rings to cromakalim

The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride (NaCl) per kilogram (kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) pump activity was measured by potassium (K+)-induced relaxation (with or without ouabain) following precontraction with 10(-7) M noradrenaline. The KATP channel was studied by measuring the relaxation response to cromakalim, precontracted with either 10(-7) M noradrenaline or 60 mM potassium chloride (KCl). The Na-K ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K(+)-induced contraction. Cromakalim produced relaxation of noradrenaline-precontracted rings from the control rats; rings from salt-loaded rats showed significantly less relaxation than control (p < 0.05) under similar conditions. During K(+)-induced precontraction, cromakalim produced a weak biphasic response in the control rings--an initial relaxation and then a reversal. Cromakalim produced further contraction of K(+)-induced precontraction in the salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.

Aspectos estructurales y funcionales de la vena safena humana utilizada como puente aorto-coronario en la cirugia de revascularización miocárdica / Structural and functional aspects of the human saphenous vein used as aorto-coronary graft in myocardial revascularization

La vena safena humana (VSH) se utiliza como puente en la cirugía de revascularización coronaria y de otros lechos arteriales, especialmente de miembros inferiores. Dado que los puentes de VSH presentan un porcentaje considerable de obliteración, numerosos estudios han investigado los factores que promoverían la producción de la estenosis en los mismos. Este artículo describe resultados sobre las condiciones estructurales y funcionales que confluyen para producir la obstrucción de los puentes de VSH. Se analiza la reactividad de la VSH a agonistas fisiológicos, incluídos los factores contrayentes y relajantes derivados del endotelio, por su importancia en determinar el vasoespasmo y en modificar la expresión de factores de crecimiento tisular y/o promotores de procesos trombóticos y ateromatosos. Se describen mecanismos involucrados en la regulación del estado contráctil de los miocitos lisos, en particular la actividad de canales de K+ de la membrana

Role of ATP sensitive potassium channel on 7-hydroxy flavone induced antinociception and possible association with changes in glycaemic status.

Opioid type of analgesics open ATP sensitive potassium channel at the cellular level to produce antinociceptive response. These channels have also been shown to modulate insulin secretion by the pancreas. 7-hydroxy flavone, an antinociceptive agent shown to act through opioid pathways was investigated for its effect on glycaemic state and associated algesic state. The involvement of ATP sensitive potassium channel in the action was examined by using glybenclamide. The result reveal that 7-HF per se did not elicit any significant change in the glycaemic state simultaneously eliciting antinociceptive response as tested by acetic acid induced abdominal constriction assay procedure. Glibenclamide treatment attenuated the antinociceptive effect of 7-HF and while maintained its hypoglycaemic response. The present finding suggest that 7-HF induces antinociception like morphine, utilise ATP sensitive potassium channel at the cellular level and do not suggest a cause-effect relationship between the changes in the glycaemic and algesic state. Possibly, insulin which is controlled by ATP sensitive potassium channel at the cellular level might also modulate antinociception exhibiting a cause-effect relationship between them.

Membrane stretch increases the activity of Ca(2+)-activated K+ channels in rabbit coronary vascular smooth muscles

It has been proposed that Ca(2+)-activated K+ channels play an essential role in maintaining vascular tone during stretch of blood vessel. However, the underlying mechanism of stretch-induced change of Ca(2+)-activated K+ channel activities are still unknown. The present experiment was designed to investigate the effect of membrane stretch on these channels whose activity was measured from rabbit coronary smooth muscle cells using a patch clamp technique. Ca(2+)-activated K+ channel were identified by their Ca2+ and voltage dependencies and its large conductances as in other preparations. Perfusion of cells with a hypotonic solution, which mimics stretching the cell membrane by making a cell swelling, produced an increase in channel activity in cell-attached patch mode. The similar increase was observed when negative pressure was applied into the patch pipette for stretching the cell membrane within a patch area. In inside-out patch, stretch still increased channel activity even under the conditions which exclude the possible involvement of secondary messengers, or of transmembrane Ca2+ influx via stretch-activated cation channels. Pretreatment of arachidonic acid or albumin showed no effect on stretch-induced channel activation, excluding the possibility of fatty acids mediated channel activation during membrane stretch. These results indicate that the stretch may directly increase the activity of Ca(2+)-activated K+ channels in our experimental condition.

Sulfhydryl modification affects coronary artery tension by changing activity of delayed rectifier K+ current

It has been reported that a change in the cellular redox state may be involved in the regulation of vascular tone, but the underlying mechanism is not fully understood. The present study was designed to investigate the cellular effect of sulfhydryl modifying agents in the coronary artery of rabbit using the tension measurement and whole cell clamping method. The application of diamide, a sulfhydryl oxidizing agent, relaxed the endothelium denuded coronary arteries in a dose dependent manner. The fact that this diamide-induced relaxation was significantly attenuated by a pretreatment of 4-AP, and the coronary arteries precontracted with 100 mM K+ instead of histamine, suggests the involvement of 4-AP sensitive K+ channels in the diamide-induced relaxation of coronary arteries. Whole cell patch clamp studies revealed that the 4-AP sensitive IdK was significantly enhanced by the membrane permeant oxidizing agents, diamide and DTDP, and were reversed by subsequent exposure to the reducing agent, DTT. Neither the membrane impermeant oxidizing or reducing agents, GSSG or GSH, had any effect on the activity of IdK, indicating that intracellular sulfhydryl modification is critical for modulating IdK activity. The Diamide failed to significantly alter the voltage dependence of the activation and inactivation parameters, and did not change the inactivation process, suggesting that diamide increases the number of functional channels without altering their gating properties. Since IdK has been believed to play an important role in regulating membrane potential and arterial tone, our results about the effect of sulfhydryl modifying agents on coronary arterial tone and IdK activity should help understand the pathophysiology of the diseases, where oxidative damage has been implicated.

The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.

Bloqueo del ion bario sobre una coriente de potasio rectificadora entrante en ovocitos de rana xenopus laevis / Blockade of barium ions on inward rectifier potassium current study in frog's oocytes

Se caracterizó el efecto del ion bario (Ba²+) sobre un canal de potasio rectificador entrante endógeno (IRK-endo) de ovocitos de Xenopus laevis con la técnica de fijación de voltaje con 2 microelectrodos. Al modificar la [K+] o se provocó un cambio en el potencial de inversión y en el valor de la pendiente de la recta, tal y como se espera para una corriente predominantemente de K+. El bloqueo de IRK-endo por el Ba²+ externo presentó una baja afinidad del canal de dos formas diferentes. Una fue un bloqueo en el pico de corriente independiente de voltaje con una Kd de 0.9 ñ 0.1 mM. En contraste, un segundo efecto se observó al final del pulso (80 ms). Este bloqueo en la corriente es dependiente tanto de tiempo como de voltaje, con una Kd que muestra una dependencia de voltaje monoexponencial (t = 50 ñ 5 mV). Estos resultados sugieren la presencia de dos sitios de unión diferentes para el Ba²+; uno en la parte externa del canal y otro situado dentro del canal Nuestros resultados demuestran la existencia de canal. Nuestros resultados demuestran la existencia de una corriente endógena de K+ en ovocitos de Xenopus laevis con características semejantes a otras corrientes rectificadoras entrantes de K+ encontradas en otras especies

Canales de iones / Ions channels

Los canales de iones son glucoproteínas estructurales de la membrana celular que participan en la función, sobre todo de células excitables, para generar el potencial de acción y además ayudan a mantener el equilibrio de iones y de agua en los espacios intra y extracelulares. En la presente revisión se mencionan, entre otros aspectos, su estructura, los principios básicos de su función y algunas de las enfermedades hereditarias que ocurren habitualmente por una formación anormal de estas estructuras. La habilidad que tenemos de pensar y movernos depende de los cambios de voltaje iniciados por la movilización de iones, lo cual regula la función nerviosa y muscular. Por mucho tiempo se ha sabido que estos canales son blanco de manipulación por varios fármacos aplicados, sobre todo, a nivel de la clínica cardiovascular; otros medicamentos, usados ampliamente en forma secundaria, también pueden alterar la función de los canales induciendo efectos colaterales que pueden ser graves. Todos estos aspectos y algunos otros se mencionan en la presente revisión